L USO DELLA RISORSA ALBUMINA LA PROSPETTIVA DEL CLINICO

Transcription

1 AISF-SIMTI POSITION PAPER - L USO APPROPRIATO DELL ALBUMINA Roma, 29 marzo 2016 L USO DELLA RISORSA ALBUMINA LA PROSPETTIVA DEL CLINICO Mauro Bernardi Semeiotica Medica Dipartimento di Scienze Mediche e Chirurgiche Alma Mater Studiorum - Università di Bologna

2 DISCLOSURES CLS Behring GmbH PPTA Europe Baxter Healthcare SA Gilead Sciences consultant speaker speaker consultant speaker speaker

3 ALBUMIN CONSUMPTION WORLDWIDE YEAR 2012 Brasil India Russia Mexico Turkey Argentina UK Egypt Cina Iran Germany Sweden France Canada Japan Spain Australia USA Belgium Italy ISTISAN Report

4 ALBUMIN CONSUMPTION WORLDWIDE RELATIONSHIP WITH HEALTH EXPENDITURE Health Expend / pop (US $) ** R = 0.66; P = Albumin consumption (g / 1000 pop) * * ISTISAN Report ** The World Bank

5 Trento / Bolzano Friuli V. Giulia Marche Piemonte Veneto Liguria Emilia-Romagna Umbria Lombardia Sicilia V. d'aosta Abruzzo Molise ITALIA Basilicata Toscana Lazio Calabria Campania Puglia Sardegna ISTISAN Report ALBUMIN CONSUMPTION IN ITALY YEAR

6 Remohì et al, Ann Pharmacother 2000 INAPPROPRIATE USE OF ALBUMIN 22 public hospital in Spain (3 non consecutive days 5 mo period) Use of albumin deemed inappropriate in 76% of cases Main reasons for inappropriate use: nutritional intervention hypoalbuminemia cardiac surgery abdominal surgery nephrotic syndrome $ 140,891 expenditure (77% of total) for inappropriate use

7 RESTRAINTS FOR ALBUMIN USE Lack of solid scientific evidence Availability of cheaper alternatives High cost Limited availability Fear of transmission of viral infection

8 USE OF ALBUMIN IN LIVER DISEASE INDICATIONS EMERGING FROM EBM Prevention of post-paracentesis circulatory dysfunction (> 4-5 L of tapped ascites) Prevention 8 of g / renal L of tapped failure induced ascites by spontaneous bacterial peritonitis 1 g / Kg bw at diagnosis Hepatorenal g syndrome, / Kg g / bw day at thereafter associated diagnosis with vasopressors 1 g [terlipressin; / Kg bw on midodrine day 3 + octreotide; noradrenalin]) EASL CPGs on Tx of ascites, SBP & hepatorenal syndrome, J Hepatol 2010

9 USE OF ALBUMIN IN HRS THE ITALIAN EXPERIENCE HRS 1: 76 patients HRS 2: 40 patients Albumin + vasoconstrictors in HRS 1: 84% Albumin + vasoconstrictors in HRS 2: 72% Mean daily albumin dose: 27 ± 2 g Complete response: 30% Partial response: 20% Salerno et al, J Hepatol 2011

10 ALBUMIN USE IN PATIENTS WITH CIRRHOSIS AASLD MEMBERS SURVEY Bajaj et al, Hepatology 2015

11 ALBUMIN USE ACCORDING TO GUIDELINES THE CANONIC STUDY 1 Patients Patients receiving (N = 1343) albumin N (%) N (%) Included with follow-up* 699 (52) 425 (61) Infection (SBP 26%) 398 (57) 152 (38) Paracentesis 291 (42) 225 (77) HRS 179 (26) 75 (42) *There were patients with more than one complication associated to albumin administration. 1 Moreau et al, Gastroenterology 2013 Arroyo V Use of Albumin in the CANONIC Study

12 RESTRAINTS FOR ALBUMIN USE Lack of solid scientific evidence Availability of cheaper alternatives High cost Limited availability Fear of transmission of viral infection

13 Bernardi et al, Hepatology 2012 PREVENTION OF PICD META-ANALYSIS: MORTALITY

14 USE OF ALBUMIN IN HEPATOLOGY ARE THEY CHEAPER ALTERNATIVES? Albumin is superior to any other alternative tool (artificial plasma expanders, crystalloids, vasoconstrictors) in preventing PPCD and paracentesis-induced hyponatremia and mortality Bernardi et al, Hepatology 2012 Albumin is superior to hydroxyethyl starch in improving effective volemia in patients with SBP Fernandez et al, Hepatology 2005 Terlipressin plus albumin is superior to terlipressin alone in achieving a complete response to treatment in HRS Ortega et al, Hepatology 2002

15 RESTRAINTS FOR ALBUMIN USE Lack of solid scientific evidences Availability of cheaper alternatives High cost Limited availability Fear of transmission of viral infection

16 FIGHTING THE SCARCITY OF RESOURCES JAMA 2013; February 27, 2013

17 ALBUMIN VIALS Mirici-Cappa et al., World J Gastroent 2011 FIGHTING THE SCARCITY OF RESOURCES THE ST. ORSOLA-MALPIGHI HOSPITAL EXPERIENCE Albumin not recommended cerebral ischemia would healing nutritional 7 departments purposes neprotic 91 units syndrome 1,758 beds Albumin 72,000 admissions as 2nd line / tx y hypovolemic OLT program shock major surgery burns malabsorption syndrome YEAR

18 ALBUMIN VIALS Mirici-Cappa et al., World J Gastroent 2011 FIGHTING THE SCARCITY OF RESOURCES THE ST. ORSOLA-MALPIGHI HOSPITAL EXPERIENCE Enforcement of guidelines

19 ALBUMIN: % OF TOTAL CONSUMPTION Mirici-Cappa et al., World J Gastroent 2011 FIGHTING THE SCARCITY OF RESOURCES THE ST. ORSOLA-MALPIGHI HOSPITAL EXPERIENCE 100 Liver Units Other Units Intensive care 80 Enforcement of guidelines YEAR

20 FIGHTING THE SCARCITY OF RESOURCES MAXIMIZING BENEFITS Choose interventions and care settings that maximize benefits, minimize arms, and reduce costs (using comparative effectiveness and cost-effectiveness data) Smith et al, Ann Int Med 2012

21 FIGHTING THE SCARCITY OF RESOURCES MAXIMIZING BENEFITS Identify features (clinical, lab, biomarkers) allowing to select patients who would mostly receive benefit from albumin administration Identify the lowest effective albumin dosages and treatment durations in different settings Assess cheaper alternatives or combined treatments with (at least) equal efficacy through reliable studies Promote controlled clinical trials assessing albumin use in new indications

22 FIGHTING THE SCARCITY OF RESOURCES APPROPRIATE COST ASSESSMENT Choose interventions and care settings that maximize benefits, minimize arms, and reduce costs (using comparative effectiveness and cost-effectiveness data) Smith et al, Ann Int Med 2012

23 COST-EFFECTIVENESS OF ALBUMIN USE SEVERE SEPSIS & SEPTIC SHOCK SALINE vs ALBUMIN - 4,6% according to the SAFE study Cost /life saved: 6,037 Cost /y life saved: 617 Prevention programs in which the cost per year of gained life is less than twice the per capita GNP ( 50,000 in France) should be systematically adopted Guidet et al, J Crit Care 2007

24 PREVENTION OF RENAL FAILURE IN SBP COST ANALYSIS Albumin infusion 1,750 g = 4,655 Albumin infusion 1,110 g = 2,953 Terlipressin 186 mg = 7,043 Days in hospital 125 d = 37,500 Total cost 52, high risk SBP pts (4 with RI) + 1 RI (3 HRS) No RI: discharge after 10 d RI: discharge after 15 days Potential deaths 1 10 high risk SBP pts (4 with RI) + 3 RI (5 HRS) No RI: discharge after 10 d RI: discharge after 15 days Potential deaths 3 assumptions: 1 g Albumin = mg Terlipressin = hospital day = 300 Albumin infusion 1,850 g = 4,921 Terlipressin 330 mg = 12,495 Days in hospital 135 d = 40,500 Total cost 57,916

25 ALBUMIN vs POLYGELINE IN CIRRHOSIS EFFICACY & COST ANALYSIS Cirrhosis with ascites 30 albumin group 38 polygeline group Follow-up 6 months Inclusion criteria therapeutic paracentesis renal impairment severe hyponatremia RISK FOR DEVELOPING LIVER RELATED COMPLICATIONS* Polygeline vs Albumin: HR 1.95; 95% CI [ ], P < MEDIAN COST ADJUSTED TO A 30-DAY PERIOD Polygeline: 4,612 vs Albumin: 1,915; P < * adjustment for baseline history of portal hypertensive bleeding creatinine clearance serum albumin Moreau et al, Liver Int 2006

26 CONCLUSIONS The use of albumin for the current indications given by guidelines is variable and often sub-optimal Continuing education is still needed In order to avoid and oppose uncritical rationing of albumin use by health Authorities it would be essential: - avoid inappropriate use - refine indications and dosages - perform appropriate cost analysis - support new indications or alternative treatments with reliable studies

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